Method and device for applications of selective organ cooling

ABSTRACT

The invention provides a method and device for selectively controlling the temperature of a selected organ of a patient for performance of a specified application. The method includes introducing a guide catheter into a blood vessel. The guide catheter may have a soft tip and a retaining flange, and may be used to provide treatments such as administration of thrombolytic drug therapies, stenting procedures, angiographic procedures, etc. A supply tube is provided having a heat transfer element attached to a distal end thereof. The heat transfer element having a plurality of exterior surface irregularities, these surface irregularities having a depth greater than the boundary layer thickness of flow in the feeding artery of the selected organ. The supply tube and heat transfer element may be inserted through the guide catheter to place the heat transfer element in the feeding artery of the selected organ. Turbulence is created around the surface irregularities at a distance from the heat transfer element greater than the boundary layer thickness of flow in the feeding artery, thereby creating turbulence throughout the blood flow in the feeding artery. A working fluid is circulated into the heat transfer element via the supply tube and via an internal lumen of the heat transfer element. The fluid may be circulated out of the heat transfer element via an external lumen of the heat transfer element and through the guide catheter. Heat is thereby transferred between the heat transfer element and the blood in the feeding artery to selectively control the temperature of the selected organ during or soon before or after the specified application.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This is a divisional patent application of co-pending U.S. patentapplication Ser. No. 09/215,040 filed on Dec. 16, 1998, and entitled“Method and Device for Applications of Selective Organ Cooling” which isa continuation-in-part patent application of co-pending U.S. patentapplications: Ser. No. 09/103,342, filed on Jun. 23, 1998, and entitled“Selective Organ Cooling Catheter and Method of Using the Same”; Ser.No. 09/052,545, filed on Mar. 31, 1998, and entitled “Circulating FluidHypothermia Method and Apparatus”; Ser. No. 09/047,012, filed on Mar.24, 1998, and entitled “Improved Selective Organ Hypothermia Method andApparatus”, now U.S. Pat. No. 5,957,963 issued on Sep. 28, 1999; Ser.No. 09/215,038, filed on Dec. 16, 1998, and entitled “An InflatableCatheter for Selective Organ Heating and Cooling and Method of Using theSame”; and Ser. No. 09/215,039, filed on Dec. 16, 1998, and entitled“Method for Low Temperature Thrombolysis and Low TemperatureThrombolytic Agent with Selective Organ Control”; the entirety of eachbeing incorporated by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] Not Applicable

BACKGROUND OF THE INVENTION

[0003] 1. Field of the Invention

[0004] The present invention relates generally to the modification andcontrol of the temperature of a selected body organ. More particularly,the invention relates to applications of selective organ cooling whichadvantageously employ complementary techniques.

[0005] 2. Background Information

[0006] Organs in the human body, such as the brain, kidney and heart,are maintained at a constant temperature of approximately 37° C.Hypothermia can be clinically defined as a core body temperature of 35°C. or less. Hypothermia is sometimes characterized further according toits severity. A body core temperature in the range of 33° C. to 35° C.is described as mild hypothermia. A body temperature of 28° C. to 32° C.is described as moderate hypothermia. A body core temperature in therange of 24° C. to 28° C. is described as severe hypothermia.

[0007] Hypothermia is uniquely effective in reducing brain injury causedby a variety of neurological insults and may eventually play animportant role in emergency brain resuscitation. Experimental evidencehas demonstrated that cerebral cooling improves outcome after globalischemia, focal ischemia, or traumatic brain injury. For this reason,hypothermia may be induced in order to reduce the effect of certainbodily injuries to the brain as well as other organs.

[0008] Cerebral hypothermia has traditionally been accomplished throughwhole body cooling to create a condition of total body hypothermia inthe range of 20° C. to 30° C. However, the use of total body hypothermiarisks certain deleterious systematic vascular effects. For example,total body hypothermia may cause severe derangement of thecardiovascular system, including low cardiac output, elevated systematicresistance, and ventricular fibrillation. Other side effects includerenal failure, disseminated intravascular coagulation, and electrolytedisturbances. In addition to the undesirable side effects, total bodyhypothermia is difficult to administer.

[0009] Catheters have been developed which are inserted into thebloodstream of the patient in order to induce total body hypothermia.For example, U.S. Pat. No. 3,425,419 to Dato describes a method andapparatus of lowering and raising the temperature of the human body.Dato induces moderate hypothermia in a patient using a metalliccatheter. The metallic catheter has an inner passageway through which afluid, such as water, can be circulated. The catheter is insertedthrough the femoral vein and then through the inferior vena cava as faras the right atrium and the superior vena cava. The Dato catheter has anelongated cylindrical shape and is constructed from stainless steel. Byway of example, Dato suggests the use of a catheter approximately 70 cmin length and approximately 6 mm in diameter. However, use of the Datodevice implicates the negative effects of total body hypothermiadescribed above.

[0010] Due to the problems associated with total body hypothermia,attempts have been made to provide more selective cooling. For example,cooling helmets or head gear have been used in an attempt to cool onlythe head rather than the patient's entire body. However, such methodsrely on conductive heat transfer through the skull and into the brain.One drawback of using conductive heat transfer is that the process ofreducing the temperature of the brain is prolonged. Also, it isdifficult to precisely control the temperature of the brain when usingconduction due to the temperature gradient that must be establishedexternally in order to sufficiently lower the internal temperature. Inaddition, when using conduction to cool the brain, the face of thepatient is also subjected to severe hypothermia, increasing discomfortand the likelihood of negative side effects. It is known that profoundcooling of the face can cause similar cardiovascular side effects astotal body cooling. From a practical standpoint, such devices arecumbersome and may make continued treatment of the patient difficult orimpossible.

[0011] Selected organ hypothermia has been accomplished usingextracorporeal perfusion, as detailed by Arthur E. Schwartz, M.D. etal., in Isolated Cerebral Hypothermia by Single Carotid Artery Perfusionof Extracorporeally Cooled Blood in Baboons, which appeared in Vol. 39,No. 3, NEUROSURGERY 577 (September, 1996). In this study, blood wascontinually withdrawn from baboons through the femoral artery. The bloodwas cooled by a water bath and then infused through a common carotidartery with its external branches occluded. Using this method, normalheart rhythm, systemic arterial blood pressure and arterial blood gasvalues were maintained during the hypothermia. This study showed thatthe brain could be selectively cooled to temperatures of 20° C. withoutreducing the temperature of the entire body. However, externalcirculation of blood is not a practical approach for treating humansbecause the risk of infection, need for anticoagulation, and risk ofbleeding is too great. Further, this method requires cannulation of twovessels making it more cumbersome to perform particularly in emergencysettings. Even more, percutaneous cannulation of the carotid artery isdifficult and potentially fatal due to the associated arterial walltrauma. Finally, this method would be ineffective to cool other organs,such as the kidneys, because the feeding arteries cannot be directlycannulated percutaneously.

[0012] Selective organ hypothermia has also been attempted by perfusionof a cold solution such as saline or perflourocarbons. This process iscommonly used to protect the heart during heart surgery and is referredto as cardioplegia. Perfusion of a cold solution has a number ofdrawbacks, including a limited time of administration due to excessivevolume accumulation, cost, and inconvenience of maintaining theperfusate and lack of effectiveness due to the temperature dilution fromthe blood. Temperature dilution by the blood is a particular problem inhigh blood flow organs such as the brain.

BRIEF SUMMARY OF THE INVENTION

[0013] The invention provides a practical method and apparatus whichmodifies and controls the temperature of a selected organ and which maybe used in combination with many complementary therapeutic techniques.

[0014] In one aspect, the invention is directed to a method forselectively controlling the temperature of a selected organ of a patientfor performance of a specified application. The method includesintroducing a guide catheter into a blood vessel and providing a supplytube having a heat transfer element attached to a distal end thereof.The heat transfer element has a plurality of exterior surfaceirregularities, the surface irregularities having a depth greater thanthe boundary layer thickness of flow in the feeding artery of theselected organ. The supply tube and heat transfer element are insertedthrough the guide catheter to place the heat transfer element in thefeeding artery of the selected organ. Turbulence is created around thesurface irregularities at a distance from the heat transfer elementgreater than the boundary layer thickness of flow in the feeding artery,thereby creating turbulence throughout the blood flow in the feedingartery. A working fluid is circulated into the heat transfer element viathe supply tube. The working fluid is circulated out of the heattransfer element via the guide catheter. Heat is thereby transferredbetween the heat transfer element and the blood in the feeding artery toselectively control the temperature of the selected organ.

[0015] Implementations of the invention may include one or more of thefollowing. The surface irregularities on the heat transfer element mayinclude a plurality of segments of helical ridges and grooves havingalternating directions of helical rotation. Turbulence may be created byestablishing repetitively alternating directions of helical blood flowwith the alternating helical rotations of the ridges and grooves, andmay be induced for greater than 20% of the period of the cardiac cyclewithin the carotid artery.

[0016] In another aspect, the invention relates to a method forselective thrombolysis by selective vessel hypothermia. The methodincludes introducing a guide catheter into a thrombosed blood vessel,delivering a thrombolytic drug to the blood by flowing the thrombolyticdrug into the guide catheter, and introducing a supply tube having aheat transfer element at a distal end thereof into the thrombosed bloodvessel through the guide catheter. The heat transfer element is cooledby flowing a working fluid through the heat transfer element, the returnpath for the working fluid being the guide catheter. The blood isthereby cooled to a prespecified temperature by flowing the blood pastthe heat transfer element. The system may also be used to heat the bloodfor hyperthermia applications.

[0017] Implementations of the invention may include one or more of thefollowing. The drug may be chosen from the group consisting of tPA,urokinase, streptokinase, precursors of urokinase, and combinationsthereof. For hypothermia applications, if the thrombolytic drug isstreptokinase, the prespecified temperature range may be between about30° C. and 32° C. If the thrombolytic drug is urokinase or a precursorto urokinase, the prespecified temperature range may be below about 28°C. For hyperthermia applications, if the thrombolytic drug is tPA, theprespecified temperature range may be between about 37° C. to 40° C.

[0018] In another aspect, the invention is directed to a selective organheat transfer device and guide catheter assembly. The assembly includesa guide catheter capable of insertion to a selected feeding artery inthe vascular system of a patient, the guide catheter having a soft tipand an interior retaining flange at a distal end. The assembly alsoincludes a flexible supply tube capable of insertion in the guidecatheter and a heat transfer element attached to a distal end of thesupply tube. The heat transfer element has a flange at a distal end, theflange capable of engagement with the retaining flange to prevent theheat transfer element from disengaging with the guide catheter. Aplurality of exterior surface irregularities are disposed on the heattransfer element, the surface irregularities being shaped and arrangedto create turbulence in surrounding fluid, the surface irregularitieshaving a depth at least equal to the boundary layer thickness of flow inthe feeding artery.

[0019] Implementations of the invention include one or more of thefollowing. A strut may be coupled to the supply tube at a distal endthereof. The heat transfer element may include a plurality of heattransfer segments, and may further include a flexible joint connectingeach of the heat transfer segments to adjacent the heat transfersegments. The flexible joint may be a bellows, a metal tube, a plastictube, a rubber tube, a latex rubber tube, etc.

[0020] In another aspect, the invention is directed to a method forperforming angiography during selective vessel hypothermia. The methodincludes introducing a guide catheter into a blood vessel and deliveringa radioopaque fluid to the blood by flowing the radioopaque fluid intothe guide catheter. A supply tube having a heat transfer element at adistal end thereof is introduced into the blood vessel through the guidecatheter. The heat transfer element is cooled by flowing a working fluidthrough the heat transfer element, the return path for the working fluidbeing the guide catheter. Blood is thereby cooled by flowing past theheat transfer element. Thus, the cooling can occur at or near the sametime as angiography.

[0021] In another aspect, the invention is directed to a method forperforming stenting of a stenotic lesion during selective vesselhypothermia. The method includes introducing a guide catheter into ablood vessel and introducing a guide wire through the guide catheter andacross a stenotic lesion. A balloon catheter loaded with a stent is thendelivered via the guide wire such that the stent is positioned acrossthe lesion. The balloon is expanded with contrast, after which the stentmay be deployed. The heat transfer element and supply tube may then beemployed to cool the blood as described above. Similarly, the coolingcan occur at or near the same time as the stenting procedure.

[0022] In another aspect of the invention, a return catheter may becoupled to a heat transfer element, distal end of the heat transferelement defining a hole. The return catheter and heat transfer elementmay together form a “guide catheter” through which may be placed a guidewire, a microcatheter, etc. In particular, a catheter may be placedtherein having a tapered shape such that the catheter lodges into thehole. The catheter may have an outlet at a distal end to allow drugdelivery, an outlet upstream of the distal end to allow delivery of aworking fluid to the interior of the heat transfer element, or in somecases both.

[0023] Advantages of the invention include the following. The device maybe placed in an artery without traumatizing the arterial wall and withdamaging the device itself. The device may be placed in an artery simplyand by a variety of practitioners such as cardiologists orneurosurgeons. The device allows the complementary performance ofsimultaneous procedures along with brain cooling, these proceduresincluding angiography, stenotic lesion stenting, and drug delivery.

[0024] The novel features of this invention, as well as the inventionitself, will be best understood from the attached drawings, taken alongwith the following description, in which similar reference charactersrefer to similar parts, and in which:

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0025]FIG. 1 is an elevation view of a turbulence inducing heat transferelement within an artery;

[0026]FIG. 2 is an elevation view of one embodiment of a heat transferelement which may be employed according to the invention;

[0027]FIG. 3 is longitudinal section view of the heat transfer elementof FIG. 2;

[0028]FIG. 4 is a transverse section view of the heat transfer elementof FIG. 2;

[0029]FIG. 5 is a perspective view of the heat transfer element of FIG.2 in use within a blood vessel;

[0030]FIG. 6 is a cut-away perspective view of an alternative embodimentof a heat transfer element which may be employed according to theinvention;

[0031]FIG. 7 is a transverse section view of the heat transfer elementof FIG. 6;

[0032]FIG. 8 is a schematic representation of the invention being usedin one embodiment to cool the brain of a patient;

[0033]FIG. 9 is a cross-section of a guide catheter which may beemployed for applications of the invention;

[0034]FIG. 10 is a schematic representation of the invention being usedwith a return tube/guide catheter;

[0035]FIG. 11 is a schematic representation of the invention being usedwith a delivery catheter;

[0036]FIG. 12 is a schematic representation of the invention being usedwith a working fluid catheter;

[0037]FIG. 13 is a schematic representation of the invention being usedwith a guide wire;

[0038]FIG. 14 is a schematic representation of the invention being usedwith a delivery/working fluid catheter with a balloon attachment; and

[0039]FIG. 15 is a second schematic representation of the inventionbeing used with a delivery/working fluid catheter with a balloonattachment.

DETAILED DESCRIPTION OF THE INVENTION

[0040] The temperature of a selected organ may be intravascularlyregulated by a heat transfer element placed in the organ's feedingartery to absorb or deliver heat to or from the blood flowing into theorgan. While the method is described with respect to blood flow into anorgan, it is understood that heat transfer within a volume of tissue isanalogous. In the latter case, heat transfer is predominantly byconduction.

[0041] The heat transfer may cause either a cooling or a heating of theselected organ. A heat transfer element that selectively alters thetemperature of an organ should be capable of providing the necessaryheat transfer rate to produce the desired cooling or heating effectwithin the organ to achieve a desired temperature.

[0042] The heat transfer element should be small and flexible enough tofit within the feeding artery while still allowing a sufficient bloodflow to reach the organ in order to avoid ischemic organ damage. Feedingarteries, like the carotid artery, branch off the aorta at variouslevels. Subsidiary arteries continue to branch off these initialbranches. For example, the internal carotid artery branches off thecommon carotid artery near the angle of the jaw. The heat transferelement is typically inserted into a peripheral artery, such as thefemoral artery, using a guide catheter or guide wire, and accesses afeeding artery by initially passing though a series of one or more ofthese branches. Thus, the flexibility and size, e.g., the diameter, ofthe heat transfer element are important characteristics. Thisflexibility is achieved as is described in more detail below.

[0043] These points are illustrated using brain cooling as an example.The common carotid artery supplies blood to the head and brain. Theinternal carotid artery branches off the common carotid artery to supplyblood to the anterior cerebrum. The heat transfer element may be placedinto the common carotid artery or into both the common carotid arteryand the internal carotid artery.

[0044] The benefits of hypothermia described above are achieved when thetemperature of the blood flowing to the brain is reduced to between 30°C. and 32° C. A typical brain has a blood flow rate through each carotidartery (right and left) of approximately 250-375 cubic centimeters perminute (cc/min). With this flow rate, calculations show that the heattransfer element should absorb approximately 75-175 watts of heat whenplaced in one of the carotid arteries to induce the desired coolingeffect. Smaller organs may have less blood flow in their respectivesupply arteries and may require less heat transfer, such as about 25watts.

[0045] The method employs conductive and convective heat transfers. Oncethe materials for the device and a working fluid are chosen, theconductive heat transfers are solely dependent on the temperaturegradients. Convective heat transfers, by contrast, also rely on themovement of fluid to transfer heat. Forced convection results when theheat transfer surface is in contact with a fluid whose motion is induced(or forced) by a pressure gradient, area variation, or other such force.In the case of arterial flow, the beating heart provides an oscillatorypressure gradient to force the motion of the blood in contact with theheat transfer surface. One of the aspects of the device uses turbulenceto enhance this forced convective heat transfer.

[0046] The rate of convective heat transfer Q is proportional to theproduct of S, the area of the heat transfer element in direct contactwith the fluid, ΔT=T _(b) −T _(s), the temperature differential betweenthe surface temperature T_(s), of the heat transfer element and the freestream blood temperature T_(b), and {overscore (h)}_(c), the averageconvection heat transfer coefficient over the heat transfer area.{overscore (h)}_(c) is sometimes called the “surface coefficient of heattransfer” or the “convection heat transfer coefficient”.

[0047] The magnitude of the heat transfer rate Q to or from the fluidflow can be increased through manipulation of the above threeparameters. Practical constraints limit the value of these parametersand how much they can be manipulated. For example, the internal diameterof the common carotid artery ranges from 6 to 8 mm. Thus, the heattransfer element residing therein may not be much larger than 4 mm indiameter to avoid occluding the vessel. The length of the heat transferelement should also be limited. For placement within the internal andcommon carotid artery, the length of the heat transfer element islimited to about 10 cm. This estimate is based on the length of thecommon carotid artery, which ranges from 8 to 12 cm.

[0048] Consequently, the value of the surface area S is limited by thephysical constraints imposed by the size of the artery into which thedevice is placed. Surface features, such as fins, can be used toincrease the surface area of the heat transfer element, however, thesefeatures alone cannot provide enough surface area enhancement to meetthe required heat transfer rate to effectively cool the brain.

[0049] One may also attempt to vary the magnitude of the heat transferrate by varying ΔT. The value of ΔT=T _(b) −T _(s) can be varied byvarying the surface temperature T_(s) of the heat transfer element. Theallowable surface temperature of the heat transfer element is limited bythe characteristics of blood. The blood temperature is fixed at about37° C., and blood freezes at approximately 0° C. When the bloodapproaches freezing, ice emboli may form in the blood which may lodgedownstream, causing serious ischemic injury. Furthermore, reducing thetemperature of the blood also increases its viscosity which results in asmall decrease in the value of {overscore (h)}_(c). Increased viscosityof the blood may further result in an increase in the pressure dropwithin the artery, thus compromising the flow of blood to the brain.Given the above constraints, it is advantageous to limit the surfacetemperature of the heat transfer element to approximately 1° C.-5° C.,thus resulting in a maximum temperature differential between the bloodstream and the heat transfer element of approximately 32° C.-36° C.

[0050] One may also attempt to vary the magnitude of the heat transferrate by varying {overscore (h)}_(c). Fewer constraints are imposed onthe value of the convection heat transfer coefficient {overscore(h)}_(c). The mechanisms by which the value of {overscore (h)}_(c) maybe increased are complex. However, one way to increase {overscore(h)}_(c) for a fixed mean value of the velocity is to increase the levelof turbulent kinetic energy in the fluid flow.

[0051] The heat transfer rate Q_(no-flow) in the absence of fluid flowis proportional to ΔT, the temperature differential between the surfacetemperature T_(s) of the heat transfer element and the free stream bloodtemperature T_(b) times k, the diffusion constant, and is inverselyproportion to δ, the thickness of the boundary layer.

[0052] The magnitude of the enhancement in heat transfer by fluid flowcan be estimated by taking the ratio of the heat transfer rate withfluid flow to the heat transfer rate in the absence of fluid flowN=Q_(flow)/Q_(no-flow)={overscore (h)}_(c)/(k/δ). This ratio is calledthe Nusselt number (“Nu”). For convective heat transfer between bloodand the surface of the heat transfer element, Nusselt numbers of 30-80have been found to be appropriate for selective cooling applications ofvarious organs in the human body. Nusselt numbers are generallydependent on several other numbers: the Reynolds number, the Womersleynumber, and the Prandtl number.

[0053] Stirring-type mechanisms, which abruptly change the direction ofvelocity vectors, may be utilized to induce turbulent kinetic energy andincrease the heat transfer rate. The level of turbulence so created ischaracterized by the turbulence intensity θ. Turbulence intensity θ isdefined as the root mean square of the fluctuating velocity divided bythe mean velocity. Such mechanisms can create high levels of turbulenceintensity in the free stream, thereby increasing the heat transfer rate.This turbulence intensity should ideally be sustained for a significantportion of the cardiac cycle, and should ideally be created throughoutthe free stream and not just in the boundary layer.

[0054] Turbulence does occur for a short period in the cardiac cycleanyway. In particular, the blood flow is turbulent during a smallportion of the descending systolic flow. This portion is less than 20%of the period of the cardiac cycle. If a heat transfer element is placedco-axially inside the artery, the heat transfer rate will be enhancedduring this short interval. For typical of these fluctuations, theturbulence intensity is at least 0.05. In other words, the instantaneousvelocity fluctuations deviate from the mean velocity by at least 5%.Although ideally turbulence is created throughout the entire period ofthe cardiac cycle, the benefits of turbulence are obtained if theturbulence is sustained for 75%, 50% or even as low as 30% or 20% of thecardiac cycle.

[0055] One type of turbulence-inducing heat transfer element which maybe advantageously employed to provide heating or cooling of an organ orvolume is described in co-pending U.S. patent application Ser. No.09/103,342 to Dobak and Lasheras for a “Selective Organ Cooling Catheterand Method of Using the Same,” incorporated by reference above. In thatapplication, and as described below, the heat transfer element is madeof a high thermal conductivity material, such as metal. The use of ahighly thermally conductive material increases the heat transfer ratefor a given temperature differential between the coolant within the heattransfer element and the blood. This facilitates the use of a highertemperature coolant within the heat transfer element, allowing safercoolants, such as water, to be used. Highly thermally conductivematerials, such as metals, tend to be rigid. In that application,bellows provided a high degree of articulation that compensated for theintrinsic stiffness of the metal. In an application incorporated byreference above, the bellows are replaced with a straight metal tubehaving a predetermined thickness to allow flexibility via bending of themetal. Alternatively, the bellows may be replaced with a polymer tube,e.g., a latex rubber tube, a plastic tube, or a flexible plasticcorrugated tube.

[0056] The device size may be minimized, e.g., less than 4 mm, toprevent blockage of the blood flowing in the artery. The design of theheat transfer element should facilitate flexibility in an inherentlyinflexible material.

[0057] To create the desired level of turbulence intensity in the bloodfree stream during the whole cardiac cycle, one embodiment of the deviceuses a modular design. This design creates helical blood flow andproduces a high level of turbulence in the free stream by periodicallyforcing abrupt changes in the direction of the helical blood flow. FIG.1 is a perspective view of such a turbulence inducing heat transferelement within an artery. Turbulent flow would be found at point 114, inthe free stream area. The abrupt changes in flow direction are achievedthrough the use of a series of two or more heat transfer segments, eachcomprised of one or more helical ridges. To affect the free stream, thedepth of the helical ridge is larger than the thickness of the boundarylayer which would develop if the heat transfer element had a smoothcylindrical surface.

[0058] The use of periodic abrupt changes in the helical direction ofthe blood flow in order to induce strong free stream turbulence may beillustrated with reference to a common clothes washing machine. Therotor of a washing machine spins initially in one direction causinglaminar flow. When the rotor abruptly reverses direction, significantturbulent kinetic energy is created within the entire wash basin as thechanging currents cause random turbulent motion within the clothes-waterslurry.

[0059]FIG. 2 is an elevation view of one embodiment of a heat transferelement 14. The heat transfer element 14 is comprised of a series ofelongated, articulated segments or modules 20, 22, 24. Three suchsegments are shown in this embodiment, but two or more such segmentscould be used. As seen in FIG. 2, a first elongated heat transfersegment 20 is located at the proximal end of the heat transfer element14. A turbulence-inducing exterior surface of the segment 20 comprisesfour parallel helical ridges 28 with four parallel helical grooves 26therebetween. One, two, three, or more parallel helical ridges 28 couldalso be used. In this embodiment, the helical ridges 28 and the helicalgrooves 26 of the heat transfer segment 20 have a left hand twist,referred to herein as a counter-clockwise spiral or helical rotation, asthey proceed toward the distal end of the heat transfer segment 20.

[0060] The first heat transfer segment 20 is coupled to a secondelongated heat transfer segment 22 by a first tube section 25, whichprovides flexibility. The second heat transfer segment 22 comprises oneor more helical ridges 32 with one or more helical grooves 30therebetween. The ridges 32 and grooves 30 have a right hand, orclockwise, twist as they proceed toward the distal end of the heattransfer segment 22. The second heat transfer segment 22 is coupled to athird elongated heat transfer segment 24 by a second tube section 27.The third heat transfer segment 24 comprises one or more helical ridges36 with one or more helical grooves 34 therebetween. The helical ridge36 and the helical groove 34 have a left hand, or counter-clockwise,twist as they proceed toward the distal end of the heat transfer segment24. Thus, successive heat transfer segments 20, 22, 24 of the heattransfer element 14 alternate between having clockwise andcounterclockwise helical twists. The actual left or right hand twist ofany particular segment is immaterial, as long as adjacent segments haveopposite helical twist.

[0061] In addition, the rounded contours of the ridges 28, 32, 36 alsoallow the heat transfer element 14 to maintain a relatively atraumaticprofile, thereby minimizing the possibility of damage to the bloodvessel wall. A heat transfer element may be comprised of two, three, ormore heat transfer segments.

[0062] The tube sections 25, 27 are formed from seamless and nonporousmaterials, such as metal, and therefore are impermeable to gas, whichcan be particularly important, depending on the type of working fluidwhich is cycled through the heat transfer element 14. The structure ofthe tube sections 25, 27 allows them to bend, extend and compress, whichincreases the flexibility of the heat transfer element 14 so that it ismore readily able to navigate through blood vessels. The tube sections25, 27 are also able to tolerate cryogenic temperatures without a lossof performance. The tube sections 25, 27 may have a predeterminedthickness of their walls, such as between about 0.5 and 0.8 mils. Thepredetermined thickness is to a certain extent dependent on the diameterof the overall tube. Thicknesses of 0.5 to 0.8 mils may be appropriateespecially for a tubal diameter of about 4 mm. For smaller diameters,such as about 3.3 mm, larger thicknesses may be employed for higherstrength. In another embodiment, tube sections 25, 27 may be formed froma polymer material such as rubber, e.g., latex rubber.

[0063] The exterior surfaces of the heat transfer element 14 can be madefrom metal except in flexible joint embodiment where the surface may becomprised of a polymer material. The metal may be a very high thermalconductivity material such as nickel, thereby facilitating efficientheat transfer. Alternatively, other metals such as stainless steel,titanium, aluminum, silver, copper and the like, can be used, with orwithout an appropriate coating or treatment to enhance biocompatibilityor inhibit clot formation. Suitable biocompatible coatings include,e.g., gold, platinum or polymer paralyene. The heat transfer element 14may be manufactured by plating a thin layer of metal on a mandrel thathas the appropriate pattern. In this way, the heat transfer element 14may be manufactured inexpensively in large quantities, which is animportant feature in a disposable medical device.

[0064] Because the heat transfer element 14 may dwell within the bloodvessel for extended periods of time, such as 24-48 hours or even longer,it may be desirable to treat the surfaces of the heat transfer element14 to avoid clot formation. One means by which to prevent thrombusformation is to bind an antithrombogenic agent to the surface of theheat transfer element 14. For example, heparin is known to inhibit clotformation and is also known to be useful as a biocoating. Alternatively,the surfaces of the heat transfer element 14 may be bombarded with ionssuch as nitrogen. Bombardment with nitrogen can harden and smooth thesurface and, thus prevent adherence of clotting factors to the surface.

[0065]FIG. 3 is a longitudinal sectional view of the heat transferelement 14, taken along line 3-3 in FIG. 2. Some interior contours areomitted for purposes of clarity. An inner tube 42 creates an innercoaxial lumen 42 and an outer coaxial lumen 46 within the heat transferelement 14. Once the heat transfer element 14 is in place in the bloodvessel, a working fluid such as saline or other aqueous solution may becirculated through the heat transfer element 14. Fluid flows up a supplycatheter into the inner coaxial lumen 40. At the distal end of the heattransfer element 14, the working fluid exits the inner coaxial lumen 40and enters the outer lumen 46. As the working fluid flows through theouter lumen 46, heat is transferred from the working fluid to theexterior surface 37 of the heat transfer element 14. Because the heattransfer element 14 is constructed from a high conductivity material,the temperature of its exterior surface 37 may reach very close to thetemperature of the working fluid. The tube 42 may be formed as aninsulating divider to thermally separate the inner lumen 40 from theouter lumen 46. For example, insulation may be achieved by creatinglongitudinal air channels in the wall of the insulating tube 42.Alternatively, the insulating tube 42 may be constructed of anon-thermally conductive material like polytetrafluoroethylene or someother polymer.

[0066] It is important to note that the same mechanisms that govern theheat transfer rate between the exterior surface 37 of the heat transferelement 14 and the blood also govern the heat transfer rate between theworking fluid and the interior surface 38 of the heat transfer element14. The heat transfer characteristics of the interior surface 38 areparticularly important when using water, saline or other fluid whichremains a liquid as the coolant. Other coolants such as freon undergonucleate boiling and create turbulence through a different mechanism.Saline is a safe coolant because it is non-toxic, and leakage of salinedoes not result in a gas embolism, which could occur with the use ofboiling refrigerants. Since turbulence in the coolant is enhanced by theshape of the interior surface 38 of the heat transfer element 14, thecoolant can be delivered to the heat transfer element 14 at a warmertemperature and still achieve the necessary heat transfer rate.

[0067] This has a number of beneficial implications in the need forinsulation along the catheter shaft length. Due to the decreased needfor insulation, the catheter shaft diameter can be made smaller. Theenhanced heat transfer characteristics of the interior surface of theheat transfer element 14 also allow the working fluid to be delivered tothe heat transfer element 14 at lower flow rates and lower pressures.High pressures may make the heat transfer element stiff and cause it topush against the wall of the blood vessel, thereby shielding part of theexterior surface 37 of the heat transfer element 14 from the blood.Because of the increased heat transfer characteristics achieved by thealternating helical ridges 28, 32, 36, the pressure of the working fluidmay be as low as 5 atmospheres, 3 atmospheres, 2 atmospheres or evenless than 1 atmosphere.

[0068]FIG. 4 is a transverse sectional view of the heat transfer element14, taken at a location denoted by the line 4-4 in FIG. 2. FIG. 4illustrates a five-lobed embodiment, whereas FIG. 2 illustrates afour-lobed embodiment. As mentioned earlier, any number of lobes mightbe used. In FIG. 4, the coaxial construction of the heat transferelement 14 is clearly shown. The inner coaxial lumen 40 is defined bythe insulating coaxial tube 42. The outer lumen 46 is defined by theexterior surface of the insulating coaxial tube 42 and the interiorsurface 38 of the heat transfer element 14. In addition, the helicalridges 32 and helical grooves 30 may be seen in FIG. 4. As noted above,in the preferred embodiment, the depth of the grooves, d_(i), is greaterthan the boundary layer thickness which would have developed if acylindrical heat transfer element were introduced. For example, in aheat transfer element 14 with a 4 mm outer diameter, the depth of theinvaginations, d_(i), may be approximately equal to 1 mm if designed foruse in the carotid artery. Although FIG. 4 shows four ridges and fourgrooves, the number of ridges and grooves may vary. Thus, heat transferelements with 1, 2, 3, 4, 5, 6, 7, 8 or more ridges are specificallycontemplated.

[0069]FIG. 5 is a perspective view of a heat transfer element 14 in usewithin a blood vessel, showing only one helical lobe per segment forpurposes of clarity. Beginning from the proximal end of the heattransfer element (not shown in FIG. 5), as the blood moves forwardduring the systolic pulse, the first helical heat transfer segment 20induces a counter-clockwise rotational inertia to the blood. As theblood reaches the second segment 22, the rotational direction of theinertia is reversed, causing turbulence within the blood. Further, asthe blood reaches the third segment 24, the rotational direction of theinertia is again reversed. The sudden changes in flow direction activelyreorient and randomize the velocity vectors, thus ensuring turbulencethroughout the bloodstream. During turbulent flow, the velocity vectorsof the blood become more random and, in some cases, become perpendicularto the axis of the artery. In addition, as the velocity of the bloodwithin the artery decreases and reverses direction during the cardiaccycle, additional turbulence is induced and turbulent motion issustained throughout the duration of each pulse through the samemechanisms described above.

[0070] Thus, a large portion of the volume of warm blood in the vesselis actively brought in contact with the heat transfer element 14, whereit can be cooled by direct contact rather than being cooled largely byconduction through adjacent laminar layers of blood. As noted above, thedepth of the grooves 26, 30, 34 (FIG. 2) is greater than the depth ofthe boundary layer which would develop if a straight-walled heattransfer element were introduced into the blood stream. In this way,free stream turbulence is induced. In the preferred embodiment, in orderto create the desired level of turbulence in the entire blood streamduring the whole cardiac cycle, the heat transfer element 14 creates aturbulence intensity greater than about 0.05. The turbulence intensitymay be greater than 0.05, 0.06, 0.07 or up to 0.10 or 0.20 or greater.

[0071] Referring back to FIG. 2, the heat transfer element 14 has beendesigned to address all of the design criteria discussed above. First,the heat transfer element 14 is flexible and is made of a highlyconductive material. The flexibility is provided by a segmentaldistribution of tube sections 25, 27 which provide an articulatingmechanism. The tube sections have a predetermined thickness whichprovides sufficient flexibility. Second, the exterior surface area 37has been increased through the use of helical ridges 28, 32, 36 andhelical grooves 26, 30, 34. The ridges also allow the heat transferelement 14 to maintain a relatively atraumatic profile, therebyminimizing the possibility of damage to the vessel wall. Third, the heattransfer element 14 has been designed to promote turbulent kineticenergy both internally and externally. The modular or segmental designallows the direction of the invaginations to be reversed betweensegments. The alternating helical rotations create an alternating flowthat results in mixing the blood in a manner analogous to the mixingaction created by the rotor of a washing machine that switchesdirections back and forth. This mixing action is intended to promotehigh level turbulent kinetic energy to enhance the heat transfer rate.The alternating helical design also causes beneficial mixing, orturbulent kinetic energy, of the working fluid flowing internally.

[0072]FIG. 6 is a cut-away perspective view of an alternative embodimentof a heat transfer element 50. An external surface 52 of the heattransfer element 50 is covered with a series of axially staggeredprotrusions 54. The staggered nature of the outer protrusions 54 isreadily seen with reference to FIG. 7 which is a transversecross-sectional view taken at a location denoted by the line 7-7 in FIG.6. In order to induce free stream turbulence, the height, d_(p), of thestaggered outer protrusions 54 is greater than the thickness of theboundary layer which would develop if a smooth heat transfer element hadbeen introduced into the blood stream. As the blood flows along theexternal surface 52, it collides with one of the staggered protrusions54 and a turbulent wake flow is created behind the protrusion. As theblood divides and swirls along side of the first staggered protrusion54, its turbulent wake encounters another staggered protrusion 54 withinits path preventing the re-lamination of the flow and creating yet moreturbulence. In this way, the velocity vectors are randomized andturbulence is created not only in the boundary layer but throughout thefree stream. As is the case with the preferred embodiment, this geometryalso induces a turbulent effect on the internal coolant flow.

[0073] A working fluid is circulated up through an inner coaxial lumen56 defined by an insulating coaxial tube 58 to a distal tip of the heattransfer element 50. The working fluid then traverses an outer coaxiallumen 60 in order to transfer heat to the exterior surface 52 of theheat transfer element 50. The inside surface of the heat transferelement 50 is similar to the exterior surface 52, in order to induceturbulent flow of the working fluid. The inner protrusions can bealigned with the outer protrusions 54, as shown in FIG. 7, or they canbe offset from the outer protrusions 54, as shown in FIG. 6.

[0074]FIG. 8 is a schematic representation of the invention being usedto cool the brain of a patient. The selective organ hypothermiaapparatus shown in FIG. 8 includes a working fluid supply 10, preferablysupplying a chilled liquid such as water, alcohol or a halogenatedhydrocarbon, a supply catheter 12 and the heat transfer element 14. Thesupply catheter 12 has a coaxial construction. An inner coaxial lumenwithin the supply catheter 12 receives coolant from the working fluidsupply 10. The coolant travels the length of the supply catheter 12 tothe heat transfer element 14 which serves as the cooling tip of thecatheter. At the distal end of the heat transfer element 14, the coolantexits the insulated interior lumen and traverses the length of the heattransfer element 14 in order to decrease the temperature of the heattransfer element 14. The coolant then traverses an outer lumen of thesupply catheter 12 so that it may be disposed of or recirculated. Thesupply catheter 12 is a flexible catheter having a diameter sufficientlysmall to allow its distal end to be inserted percutaneously into anaccessible artery such as the femoral artery of a patient as shown inFIG. 8. The supply catheter 12 is sufficiently long to allow the heattransfer element 14 at the distal end of the supply catheter 12 to bepassed through the vascular system of the patient and placed in theinternal carotid artery or other small artery. The method of insertingthe catheter into the patient and routing the heat transfer element 14into a selected artery is well known in the art.

[0075] Although the working fluid supply 10 is shown as an exemplarycooling device, other devices and working fluids may be used. Forexample, in order to provide cooling, freon, perflourocarbon, water, orsaline may be used, as well as other such coolants.

[0076] The heat transfer element can absorb or provide over 75 Watts ofheat to the blood stream and may absorb or provide as much as 100 Watts,150 Watts, 170 Watts or more. For example, a heat transfer element witha diameter of 4 mm and a length of approximately 10 cm using ordinarysaline solution chilled so that the surface temperature of the heattransfer element is approximately 5° C. and pressurized at 2 atmospherescan absorb about 100 Watts of energy from the bloodstream. Smallergeometry heat transfer elements may be developed for use with smallerorgans which provide 60 Watts, 50 Watts, 25 Watts or less of heattransfer.

[0077] The practice of the present invention is illustrated in thefollowing non-limiting example.

Exemplary Procedure

[0078] 1. The patient is initially assessed, resuscitated, andstabilized.

[0079] 2. The procedure is carried out in an angiography suite orsurgical suite equipped with fluoroscopy.

[0080] 3. Because the catheter is placed into the common carotid artery,it is important to determine the presence of stenotic atheromatouslesions. A carotid duplex (Doppler/ultrasound) scan can quickly andnon-invasively make this determination. The ideal location for placementof the catheter is in the left carotid so this may be scanned first. Ifdisease is present, then the right carotid artery can be assessed. Thistest can be used to detect the presence of proximal common carotidlesions by observing the slope of the systolic upstroke and the shape ofthe pulsation. Although these lesions are rare, they could inhibit theplacement of the catheter. Examination of the peak blood flow velocitiesin the internal carotid can determine the presence of internal carotidartery lesions. Although the catheter is placed proximally to suchlesions, the catheter may exacerbate the compromised blood flow createdby these lesions. Peak systolic velocities greater that 130 cm/sec andpeak diastolic velocities>100 cm/sec in the internal indicate thepresence of at least 70% stenosis. Stenosis of 70% or more may warrantthe placement of a stent to open up the internal artery diameter.

[0081] 4. The ultrasound can also be used to determine the vesseldiameter and the blood flow and the catheter with the appropriatelysized heat transfer element could be selected.

[0082] 5. After assessment of the arteries, the patients inguinal regionis sterilely prepped and infiltrated with lidocaine.

[0083] 6. The femoral artery is cannulated and a guide wire may beinserted to the desired carotid artery. Placement of the guide wire isconfirmed with fluoroscopy.

[0084] 7. An angiographic catheter can be fed over the wire and contrastmedia injected into the artery to further to assess the anatomy of thecarotid.

[0085] 8. Alternatively, the femoral artery is cannulated and a 10-12.5french (f) introducer sheath is placed.

[0086] 9. A guide catheter is placed into the desired common carotidartery. If a guiding catheter is placed, it can be used to delivercontrast media directly to further assess carotid anatomy.

[0087] 10. A 10 f -12 f (3.3-4.0 mm) (approximate) cooling catheter issubsequently filled with saline and all air bubbles are removed.

[0088] 11. The cooling catheter is placed into the carotid artery viathe guiding catheter or over the guidewire. Placement is confirmed withfluoroscopy.

[0089] 12. Alternatively, the cooling catheter tip is shaped (angled orcurved approximately 45 degrees), and the cooling catheter shaft hassufficient pushability and torqueability to be placed in the carotidwithout the aid of a guide wire or guide catheter.

[0090] 13. The cooling catheter is connected to a pump circuit alsofilled with saline and free from air bubbles. The pump circuit has aheat exchange section that is immersed into a water bath and tubing thatis connected to a peristaltic pump. The water bath is chilled toapproximately 0°C.

[0091] 14. Cooling is initiated by starting the pump mechanism. Thesaline within the cooling catheter is circulated at 5 cc/sec. The salinetravels through the heat exchanger in the chilled water bath and iscooled to approximately 1° C.

[0092] 15. It subsequently enters the cooling catheter where it isdelivered to the heat transfer element. The saline is warmed toapproximately 5-7° C. as it travels along the inner lumen of thecatheter shaft to the end of the heat transfer element.

[0093] 16. The saline then flows back through the heat transfer elementin contact with the inner metallic surface. The saline is further warmedin the heat transfer element to 12-15° C., and in the process, heat isabsorbed from the blood, cooling the blood to 30° C. to 32° C.

[0094] 17. The chilled blood then goes on to chill the brain. It isestimated that 15-30 minutes will be required to cool the brain to 30 to32° C.

[0095] 18. The warmed saline travels back down the outer lumen of thecatheter shaft and back to the chilled water bath where it is cooled to1° C.

[0096] 19. The pressure drops along the length of the circuit areestimated to be 2-3 atmospheres.

[0097] 20. The cooling can be adjusted by increasing or decreasing theflow rate of the saline. Monitoring of the temperature drop of thesaline along the heat transfer element will allow the flow to beadjusted to maintain the desired cooling effect.

[0098] 21. The catheter is left in place to provide cooling for 12 to 24hours.

[0099] 22. If desired, warm saline can be circulated to promote warmingof the brain at the end of the procedure.

[0100] The invention may also be used in combination with othertechniques. For example, one technique employed to place working lumensor catheters in desired locations employs guide catheters, as mentionedabove. Referring to FIG. 9, a guide catheter 102 is shown which may beadvantageously employed in the invention. The guide catheter 102 has asoft tapered tip 104 and a retaining flange 124 at a distal end 101. Thesoft tapered tip 104 allows an atraumatic entrance of the guide catheter102 into an artery as well as a sealing function as is described in moredetail below. The retaining flange 124 may be a metallic member adheredto the guide catheter interior wall or may be integral with the materialof the tube. The retaining flange 124 further has a sealing functiondescribed in more detail below.

[0101] The guide catheter 102 may have various shapes to facilitateplacement into particular arteries. In the case of the carotid artery,the guide catheter 102 may have the shape of a hockey stick. The guidecatheter 102 may include a Pebax® tube with a Teflon® liner. The Teflon®liner provides sufficient lubricity to allow minimum friction whencomponents are pushed through the tube. A metal wire braid may also beemployed between the Pebax® tube and the Teflon® liner to providetorqueability of the guide catheter 102.

[0102] A number of procedures may be performed with the guide catheter102 in place within an artery. For example, a stent may be disposedacross a stenotic lesion in the internal carotid artery. This procedureinvolves placing a guide wire through the guide catheter 102 and acrossthe lesion. A balloon catheter loaded with a stent is then advancedalong the guide wire. The stent is positioned across the lesion. Theballoon is expanded with contrast, and the stent is deployedintravascularly to open up the stenotic lesion. The balloon catheter andthe guide wire may then be removed from the guide catheter.

[0103] A variety of treatments may pass through the guide catheter. Forexample, the guide catheter, or an appropriate lumen disposed within,may be employed to transfer contrast for diagnosis of bleeding orarterial blockage, such as for angiography. The same may further beemployed to deliver various drug therapies, e.g., to the brain. Suchtherapies may include delivery of thrombolytic drugs that lyse clotslodged in the arteries of the brain, as are further described in anapplication incorporated by reference above.

[0104] A proximal end 103 of the guide catheter 102 has a male luerconnector for mating with a y-connector 118 attached to a supply tube108. The supply tube 108 may include a braided Pebax® tube or apolyimide tube. The y-connector 118 connects to the guide catheter 102via a male/female luer connector assembly 116. The y-connector 118allows the supply tube 108 to enter the assembly and to pass through themale/female luer connector assembly 116 into the interior of the guidecatheter 102. The supply tube 108 may be disposed with an outlet at itsdistal end. The outlet of the supply tube 108 may also be used toprovide a working fluid to the interior of a heat transfer element 110.The guide catheter 102 may be employed as the return tube for theworking fluid supply in this aspect of the invention. In thisembodiment, a heat transfer element 110 is delivered to the distal end101 of the guide catheter 102 as is shown in FIG. 10.

[0105] In FIG. 10, the heat transfer element 110 is shown, nearly in aworking location, in combination with the return tube/guide catheter102. In particular, the heat transfer element 110 is shown near thedistal end 101 of the return tube/guide catheter (“RTGC”) 102. The heattransfer element 110 may be kept in place by a flange 106 on the heattransfer element 110 that abuts the retaining flange 124 on the RTGC102. Flanges 124 and 106 may also employ o-rings such as an o-ring 107shown adjacent to the flange 106. Other such sealing mechanisms ordesigns may also be used. In this way, the working fluid is preventedfrom leaking into the blood.

[0106] The supply tube 108 may connect to the heat transfer element 110(the connection is not shown) and may be employed to push the heattransfer element 1 10 through the guide catheter 102. The supply tubeshould have sufficient rigidity to accomplish this function. In analternative embodiment, a guide wire may be employed having sufficientrigidity to push both the supply tube 108 and the heat transfer element110 through the guide catheter 102. So that the supply tube 108 ispreventing from abutting its outlet against the interior of the heattransfer element 110 and thereby stopping the flow of working fluid, astrut 112 may be employed on a distal end of the supply tube 108. Thestrut 112 may have a window providing an alternative path for theflowing working fluid.

[0107] The heat transfer element 110 may employ any of the formsdisclosed above, as well as variations of those forms. For example, theheat transfer element 110 may employ alternating helical ridgesseparated by flexible joints, the ridges creating sufficient turbulenceto enhance heat transfer between a working fluid and blood in theartery. Alternatively, the heat transfer element 110 may be inflatableand may have sufficient surface area that the heat transfer due toconduction alone is sufficient to provide the requisite heat transfer.Details of the heat transfer element 110 are omitted in FIG. 10 forclarity.

[0108]FIG. 11 shows an alternate embodiment of the invention in which aheat transfer element 204 employs an internal supply catheter 216. Theheat transfer element 204 is shown with turbulence-inducinginvaginations 218 located thereon. Similar invaginations may be locatedin the interior of the heat transfer element 204 but are not shown forclarity. Further, it should be noted that the heat transfer element 204is shown with merely four invaginations. Other embodiments may employmultiple elements connected by flexible joints as is disclosed above.The single heat transfer element shown in FIG. 11 is provided merely forclarity.

[0109] A return supply catheter 202 is shown coupled to the heattransfer element 204. The return supply catheter may be coupled to theheat transfer element 204 in known fashion, and may provide a convenientreturn path for working fluid as may be provided to the heat transferelement 204 to provide temperature control of a flow or volume of blood.

[0110] A delivery catheter 216 is also shown in FIG. 11. The deliverycatheter 216 may be coupled to a y-connector at its proximal end in themanner disclosed above. The delivery catheter 216 may be freely disposedwithin the interior of the return supply catheter 202 except where it isrestrained from further longitudinal movement (in one direction) by aretaining flange 210 disposed at the distal end 208 of the heat transferelement 204. The delivery catheter 216 may be made sufficiently flexibleto secure itself within retaining flange 210, at least for a shortduration. The delivery catheter 216 may have a delivery outlet 212 at adistal end to allow delivery of a drug or other such material fortherapeutic purposes. For example, a radioopaque fluid may be dispensedfor angiography or a thrombolytic drug for thrombinolysis applications.

[0111] For applications in which it is desired to provide drainage ofthe artery, e.g., laser ablation, the delivery catheter may be pulledupstream of the retaining flange 210, exposing an annular hole in fluidcommunication with the return supply catheter 202. The return supplycatheter 202 may then be used to drain the volume adjacent the retainingflange 210.

[0112] The assembly may also perform temperature control of blood in theartery where the same is located. Such temperature control proceduresmay be performed, e.g., before or after procedures involving thedelivery catheter 216. Such a device for temperature control is shown inFIG. 12. In this figure, a working fluid catheter 222 is disposed withinthe return supply catheter 202 and the heat transfer element 204. In amanner similar to the delivery catheter 216, the working fluid cathetermay be freely disposed within the interior of the return supply catheter202 and may further be coupled to a y-connector at its proximal end inthe manner disclosed above. The working fluid catheter 222 may furtherbe made sufficiently flexible to secure itself within retaining flange210, at least for a short duration. The working fluid catheter 222 mayhave a plurality of outlets 214 to allow delivery of a working fluid.The outlets 214 are located near the distal end 224 of the working fluidcatheter 222 but somewhat upstream. In this way, the outlets 214 allowdispensation of a working fluid into the interior of the heat transferelement 204 rather than into the blood stream. The working fluidcatheter 222 may also be insulated to allow the working fluid tomaintain a desired temperature without undue heat losses to the walls ofthe working fluid catheter 222.

[0113] One way of using the same catheter as a delivery catheter and asa working fluid catheter is shown in FIGS. 14 and 15. In FIG. 14, adelivery/working fluid catheter 248 is shown in a position similar tothe respective catheters of FIGS. 11 and 12. The delivery/working fluidcatheter 248 has working fluid outlets and a delivery outlet, and isfurther equipped with a balloon 244 disposed at the distal end. Balloon244 may be inflated with a separate lumen (not shown). By retracting thedelivery/working fluid catheter 248 to the position shown in FIG. 15,the balloon 244 may be made to seal the hole defined by retaining flange210, thereby creating a fluid-tight seal so that working fluid may bedispensed from outlets 246 to heat or cool the heat transfer element204.

[0114] One method of disposing a heat transfer device within a desiredartery, such as the carotid artery, involves use of a guide wire.Referring to FIG. 13, a guide wire 232 is shown disposed within theinterior of the heat transfer element 204. The heat transfer element 204may conveniently use the hole defmed by retaining flange 210 to bethreaded onto the guide wire 232.

[0115] Numerous other therapies may then employ the return supplycatheter and heat transfer element as a “guide catheter”. For example,various laser and ultrasound ablation catheters may be disposed within.In this way, these therapeutic techniques may be employed at nearly thesame time as therapeutic temperature control, including, e.g.,neuroprotective cooling.

[0116] The invention has also been described with respect to certainembodiments. It will be clear to one of skill in the art that variationsof the embodiments may be employed in the method of the invention.Accordingly, the invention is limited only by the scope of the appendedclaims.

What is claimed is:
 1. A method for selectively controlling the temperature of a selected organ of a patient for performance of a specified application, comprising: introducing a guide catheter into a blood vessel; providing a supply tube having a heat transfer element attached to a distal end thereof, the heat transfer element having a plurality of exterior surface irregularities, the surface irregularities having a depth greater than the boundary layer thickness of flow in the feeding artery of the selected organ; inserting the supply tube and heat transfer element through the guide catheter to place the heat transfer element in the feeding artery of the selected organ; creating turbulence around the surface irregularities at a distance from the heat transfer element greater than the boundary layer thickness of flow in the feeding artery, thereby creating turbulence throughout the blood flow in the feeding artery; circulating fluid into the heat transfer element via the supply tube; circulating fluid out of the heat transfer element via the guide catheter; and transferring heat between the heat transfer element and the blood in the feeding artery to selectively control the temperature of the selected organ.
 2. A method as recited in claim 1 , wherein: the surface irregularities on the heat transfer element comprise a plurality of segments of helical ridges and grooves having alternating directions of helical rotation; and turbulence is created by establishing repetitively alternating directions of helical blood flow with the alternating helical rotations of the ridges and grooves.
 3. The method of claim 1 , further comprising inducing blood turbulence in greater than 20% of the period of the cardiac cycle within the carotid artery.
 4. A method for selective thrombolysis by selective vessel hypothermia, comprising: introducing a guide catheter into a thrombosed blood vessel; delivering a thrombolytic drug to the blood by flowing the thrombolytic drug into the guide catheter; introducing a supply tube having a heat transfer element at a distal end thereof into the thrombosed blood vessel through the guide catheter; cooling the heat transfer element by flowing a working fluid through the heat transfer element, the return path for the working fluid being the guide catheter; and cooling the blood by flowing the blood past the heat transfer element, such that the blood is cooled to a prespecified temperature range.
 5. The method of claim 4 , wherein the drug is chosen from the group consisting of tPA, urokinase, streptokinase, precursors of urokinase, and combinations thereof.
 6. The method of claim 5 , wherein the thrombolytic drug is streptokinase and the prespecified temperature range is between about 30° C. and 32° C.
 7. The method of claim 5 , wherein the thrombolytic drug is urokinase and the prespecified temperature range is below about 28° C.
 8. The method of claim 5 , wherein the thrombolytic drug is a precursor to urokinase and the prespecified temperature range is below about 28° C.
 9. A method for selective thrombolysis by selective vessel hyperthermia, comprising: introducing a guide catheter into a thrombosed blood vessel; delivering a thrombolytic drug to the blood by flowing the thrombolytic drug into the guide catheter; introducing a supply tube having a heat transfer element at a distal end thereof into the thrombosed blood vessel through the guide catheter; heating the heat transfer element by flowing a working fluid through the heat transfer element, the return path for the working fluid being the guide catheter; and heating the blood by flowing the blood past the heat transfer element, such that the blood is heated to a prespecified temperature range.
 10. The method of claim 9 , wherein the drug is chosen from the group consisting of tPA, urokinase, streptokinase, precursors of urokinase, and combinations thereof.
 11. The method of claim 10 , wherein the drug is tPA and the specified temperature range is between about 37° C. to 40° C.
 12. A selective organ heat transfer device and guide catheter assembly, comprising: a guide catheter capable of insertion to a selected feeding artery in the vascular system of a patient, the guide catheter having a soft tip and an interior retaining flange at a distal end; a flexible supply tube capable of insertion in the guide catheter; a heat transfer element attached to a distal end of the supply tube, the heat transfer element having a flange at a distal end, the flange capable of engagement with the retaining flange to prevent the heat transfer element from disengaging with the guide catheter; and a plurality of exterior surface irregularities on the heat transfer element, the surface irregularities being shaped and arranged to create turbulence in surrounding fluid, the surface irregularities having a depth at least equal to the boundary layer thickness of flow in the feeding artery.
 13. The assembly of claim 12 , further comprising a strut coupled to the supply tube at a distal end thereof.
 14. The assembly of claim 12 , wherein the heat transfer element comprises a plurality of heat transfer segments, and further comprising a flexible joint connecting each of the heat transfer segments to adjacent the heat transfer segments.
 15. The assembly of claim 14 , wherein the flexible joint comprises a joint selected from the group consisting of a bellows, a metal tube, a plastic tube, a rubber tube, and a latex rubber tube.
 16. The assembly of claim 12 , wherein: the surface irregularities comprise a helical ridge and a helical groove formed on each the heat transfer segment; and the helical ridge on each the heat transfer segment has an opposite helical twist to the helical ridges on adjacent the heat transfer segments.
 17. A method for performing angiography during selective vessel hypothermia, comprising: introducing a guide catheter into a blood vessel; delivering a radioopaque fluid to the blood by flowing the radioopaque fluid into the guide catheter; introducing a supply tube having a heat transfer element at a distal end thereof into the blood vessel through the guide catheter; cooling the heat transfer element by flowing a working fluid through the heat transfer element, the return path for the working fluid being the guide catheter; and cooling the blood by flowing the blood past the heat transfer element, such that the blood is cooled to a prespecified temperature range.
 18. A method for performing stenting of a stenotic lesion during selective vessel hypothermia, comprising: introducing a guide catheter into a blood vessel; introducing a guide wire through the guide catheter and across a stenotic lesion; delivering a balloon catheter loaded with a stent via the guide wire; positioning the stent across the lesion; expanding the balloon with contrast; deploying the stent; introducing a supply tube having a heat transfer element at a distal end thereof into the blood vessel through the guide catheter; cooling the heat transfer element by flowing a working fluid through the heat transfer element, the return path for the working fluid being the guide catheter; and cooling the blood by flowing the blood past the heat transfer element, such that the blood is cooled to a prespecified temperature range.
 19. A method for selectively controlling the temperature of a selected organ of a patient for performance of a specified application, comprising: introducing a return catheter into a blood vessel having a heat transfer element attached to a distal end thereof, the heat transfer element having a plurality of exterior surface irregularities, the surface irregularities having a depth greater than the boundary layer thickness of flow in the feeding artery of the selected organ, the heat transfer element having an outlet at a distal end thereof; inserting a working fluid catheter into the return catheter and heat transfer element such that the working fluid catheter plugs the outlet of the heat transfer element; creating turbulence around the surface irregularities at a distance from the heat transfer element greater than the boundary layer thickness of flow in the feeding artery, thereby creating turbulence throughout the blood flow in the feeding artery; circulating fluid into the heat transfer element via the working fluid catheter; circulating fluid out of the heat transfer element via the return catheter; and transferring heat between the heat transfer element and the blood in the feeding artery to selectively control the temperature of the selected organ.
 20. The method of claim 19 , further comprising: removing the working fluid catheter from the return catheter and the heat transfer element; inserting a delivery catheter into the return catheter and the heat transfer element, the delivery catheter having a delivery outlet at a distal end thereof; and delivering a drug via the delivery catheter.
 21. The method of claim 19 , wherein: the surface irregularities on the heat transfer element comprise a plurality of segments of helical ridges and grooves having alternating directions of helical rotation; and turbulence is created by establishing repetitively alternating directions of helical blood flow with the alternating helical rotations of the ridges and grooves.
 22. A method for selectively controlling the temperature of a selected organ of a patient for performance of a specified application, comprising: introducing a return catheter into a blood vessel having a heat transfer element attached to a distal end thereof, the heat transfer element having a plurality of exterior surface irregularities, the surface irregularities having a depth greater than the boundary layer thickness of flow in the feeding artery of the selected organ, the heat transfer element having an outlet at a distal end thereof; inserting a delivery/working fluid catheter into the return catheter and heat transfer element such that the delivery/working fluid catheter plugs the outlet of the heat transfer element in a first condition and an inflatable balloon coupled to a distal end of the delivery/working fluid catheter plugs the outlet of the heat transfer element in a second condition, the delivery/working fluid catheter having a delivery outlet at the distal end thereof and at least one working fluid outlets at a distance upstream of the distal end; creating turbulence around the surface irregularities at a distance from the heat transfer element greater than the boundary layer thickness of flow in the feeding artery, thereby creating turbulence throughout the blood flow in the feeding artery; in the first condition, circulating fluid into the heat transfer element via the working fluid catheter; circulating fluid out of the heat transfer element via the return catheter; and transferring heat between the heat transfer element and the blood in the feeding artery to selectively control the temperature of the selected organ; and in the second condition, delivering a drug to the blood via the delivery outlet in the first condition. 